title: Neural stem cells are increased after loss of β-catenin, but neural progenitors undergo cell death.
abstract: Neurons and glia in the central nervous system originate from neural stem and progenitor cells that reside in the ventricular zones. Here we examine the role of β-catenin in neural stem cell (NSC) regulation in mouse embryos lacking β-catenin specifically in the brain germinal zone. An in vitro clonal neurosphere assay was performed in order to ascertain the status of the NSC population. Intact neurospheres did not form from β-catenin-null cells due to a loss of cell adhesion and the number of expanded cells was reduced. Rescue of β-catenin expression restored adhesion and revealed that the number of NSCs increased in the knockout population. Using a clonal colony-forming assay, which confines precursor cells within a solid collagen matrix, we show that the number of NSCs in the hippocampus is unchanged although the β-catenin knockout striatum actually contains a larger proportion of NSCs. However, these colonies were smaller than those of control cells, due to increased apoptosis in the progenitor population. Furthermore, β-catenin knockout NSCs also retained multipotentiality as shown by their ability to clonally differentiate into neurons and glia. The effects on neural precursor cells were not due to loss of downstream T-cell factor signaling, as this pathway is not active in vivo in regions of the embryonic brain where NSCs and progenitor cells reside, nor is it active in vitro in NSC colonies. These data reveal that β-catenin is not required for the maintenance or differentiation of NSCs, but is required for the adhesion and survival of neural progenitor cells.
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada. tamara.holowacz@utoronto.ca
authors.forename: Tamara
authors.initials: T
authors.lastname: Holowacz
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsken
authors.forename: Daniel
authors.initials: D
authors.lastname: Dufort
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D016923:Cell Death / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051176:beta Catenin